Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet. 2006;368:387–403.

Article  CAS  PubMed  Google Scholar 

Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al. Inflammation and Alzheimer’s disease. Neurobiol Aging. 2000;21:383–421.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14:388–405.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Querfurth HW, LaFerla FM. MECHANISMS OF DISEASE Alzheimer’s disease. N. Engl J Med. 2010;362:329–44.

Article  CAS  PubMed  Google Scholar 

Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, et al. Alzheimer’s disease. Lancet. 2021;397:1577–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cummings J, Lee G, Nahed P, Kambar M, Zhong K, Fonseca J, et al. Alzheimer’s disease drug development pipeline: 2022. Alzheimer’s Dement. 2022;8:e12295.

Article  Google Scholar 

Athar T, Al Balushi K, Khan SA. Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease. Mol Biol Rep. 2021;48:5629–45.

Article  CAS  PubMed  PubMed Central  Google Scholar 

van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388:9–21.

Article  PubMed  Google Scholar 

Mintun MA, Lo AC, Duggan Evans C, Wessels AM, Ardayfio PA, Andersen SW, et al. Donanemab in early Alzheimer’s disease. N Engl J Med. 2021;384:1691–704.

Article  CAS  PubMed  Google Scholar 

Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. Jama. 2023;330:512–27.

Article  CAS  PubMed  Google Scholar 

Liu Z, Jang SW, Liu X, Cheng D, Peng J, Yepes M, et al. Neuroprotective actions of PIKE-L by inhibition of SET proteolytic degradation by asparagine endopeptidase. Mol Cell. 2008;29:665–78.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang Z, Song M, Liu X, Kang SS, Kwon IS, Duong DM, et al. Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer’s disease. Nat Med. 2014;20:1254–62.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang Z, Song M, Liu X, Su Kang S, Duong DM, Seyfried NT, et al. Delta-secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer’s disease. Nat Commun. 2015;6:8762.

Article  CAS  PubMed  Google Scholar 

Xia Y, Wang ZH, Zhang Z, Liu X, Yu SP, Wang JZ, et al. Delta- and beta- secretases crosstalk amplifies the amyloidogenic pathway in Alzheimer’s disease. Prog Neurobiol. 2021;204:102113.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Blennow K, Chen C, Cicognola C, Wildsmith KR, Manser PT, Bohorquez SMS, et al. Cerebrospinal fluid tau fragment correlates with tau PET: a candidate biomarker for tangle pathology. Brain. 2020;143:650–60.

Article  PubMed  Google Scholar 

Leuzy A, Cicognola C, Chiotis K, Saint-Aubert L, Lemoine L, Andreasen N, et al. Longitudinal tau and metabolic PET imaging in relation to novel CSF tau measures in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2019;46:1152–63.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Simrén J, Brum WS, Ashton NJ, Benedet AL, Karikari TK, Kvartsberg H, et al. CSF tau368/total-tau ratio reflects cognitive performance and neocortical tau better compared to p-tau181 and p-tau217 in cognitively impaired individuals. Alzheimer’s Res Ther. 2022;14:192.

Article  Google Scholar 

Wang ZH, Gong K, Liu X, Zhang Z, Sun X, Wei ZZ, et al. C/EBPβ regulates delta-secretase expression and mediates pathogenesis in mouse models of Alzheimer’s disease. Nat Commun. 2018;9:1784.

Article  PubMed  PubMed Central  Google Scholar 

Xia Y, Wang ZH, Zhang J, Liu X, Yu SP, Ye KX, et al. C/EBPβ is a key transcription factor for APOE and preferentially mediates ApoE4 expression in Alzheimer’s disease. Mol Psychiatry. 2021;26:6002–22.

Article  CAS  PubMed  Google Scholar 

Wang ZH, Xia Y, Liu P, Liu X, Edgington-Mitchell L, Lei K, et al. ApoE4 activates C/EBPβ/δ-secretase with 27-hydroxycholesterol, driving the pathogenesis of Alzheimer’s disease. Prog Neurobiol. 2021;202:102032.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang YA, Zhou B, Nabet AM, Wernig M, Südhof TC. Differential signaling mediated by ApoE2, ApoE3, and ApoE4 in human neurons parallels Alzheimer’s disease risk. J Neurosci. 2019;39:7408–27.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zalocusky KA, Najm R, Taubes AL, Hao Y, Yoon SY, Koutsodendris N, et al. Neuronal ApoE upregulates MHC-I expression to drive selective neurodegeneration in Alzheimer’s disease. Nat Neurosci. 2021;24:786–98.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang ZH, Xia Y, Wu Z, Kang SS, Zhang JC, Liu P, et al. Neuronal ApoE4 stimulates C/EBPβ activation, promoting Alzheimer’s disease pathology in a mouse model. Prog Neurobiol. 2022;209:102212.

Article  CAS  PubMed  Google Scholar 

Zhang Z, Obianyo O, Dall E, Du Y, Fu H, Liu X, et al. Inhibition of delta-secretase improves cognitive functions in mouse models of Alzheimer’s disease. Nat Commun. 2017;8:14740.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lei K, Kang SS, Ahn EH, Chen C, Liao J, Liu X, et al. C/EBPβ/AEP signaling regulates the oxidative stress in malignant cancers, stimulating the metastasis. Mol Cancer Ther. 2021;20:1640–52.

Article  CAS  PubMed  Google Scholar 

Zhang Z, Kang SS, Liu X, Ahn EH, Zhang Z, He L, et al. Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson’s disease. Nat Struct Mol Biol. 2017;24:632–42.

Article  PubMed  PubMed Central  Google Scholar 

Kang SS, Wu Z, Liu X, Edgington-Mitchell L, Ye K. Treating Parkinson’s disease via activation of BDNF/TrkB signaling pathways and inhibition of delta-secretase. Neurotherapeutics. 2022;19:1283–129.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liao J, Chen C, Ahn EH, Liu X, Li H, Edgington-Mitchell LE, et al. Targeting both BDNF/TrkB pathway and delta-secretase for treating Alzheimer’s disease. Neuropharmacology. 2021;197:108737.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xia Y, Wang ZH, Liu P, Edgington-Mitchell L, Liu X, Wang XC, et al. TrkB receptor cleavage by delta-secretase abolishes its phosphorylation of APP, aggravating Alzheimer’s disease pathologies. Mol Psychiatry. 2021;26:2943–63.

Article  CAS  PubMed  Google Scholar 

Qian Z, Li H, Yang H, Yang Q, Lu Z, Wang L, et al. Osteocalcin attenuates oligodendrocyte differentiation and myelination via GPR37 signaling in the mouse brain. Sci Adv. 2021;7:eabi5811.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Casali BT, Landreth GE. Abeta extraction from murine brain homogenates. Bio Protoc. 2016;6:e1787.

Article  PubMed  Google Scholar 

Sahara N, Kimura T. Biochemical properties of pathology-related tau species in tauopathy brains: an extraction protocol for tau oligomers and aggregates. Methods Mol Biol. 2018;1779:435–45.

Article  CAS  PubMed  Google Scholar 

Connor B, Young D, Yan Q, Faull RL, Synek B, Dragunow M. Brain-derived neurotrophic factor is reduced in Alzheimer’s disease. Brain Res Mol Brain Res. 1997;49:71–81.

Article  CAS  PubMed  Google Scholar 

Wang ZH, Xiang J, Liu X, Yu SP, Manfredsson FP, Sandoval IM, et al. Deficiency in BDNF/TrkB neurotrophic activity stimulates δ-secretase by upregulating C/EBPβ in Alzheimer’s disease. Cell Rep. 2019;28:655–69.e5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Devi L, Ohno M. TrkB reduction exacerbates Alzheimer’s disease-like signaling aberrations and memory deficits without affecting β-amyloidosis in 5XFAD mice. Transl Psychiatry. 2015;5:e562.

Article  CAS  PubMed